Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

2019 ◽  
Author(s):  
Benoit Visseaux ◽  
Lambert Assoumou ◽  
Nadia Mahjoub ◽  
Maxime Grude ◽  
Mary-Anne Trabaud ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Integrase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Subtype B ◽  
Recent Transmission ◽  
Increased Risk ◽  
Paris Area ◽  
Viral Subtypes ◽  
Hiv 1 ◽  
Hiv Diversity

Abstract Objectives Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016. Methods A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined. Results Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P = 0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM. Conclusions Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.

scholarly journals Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhen Wang ◽  
Bin Zhao ◽  
Minghui An ◽  
Wei Song ◽  
Xue Dong ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Hiv Infection ◽  
Northeast China ◽  
Transmitted Drug Resistance ◽  
Newly Diagnosed ◽  
Resistance Mutations ◽  
Shenyang City ◽  
Subtype B ◽  
Recent Hiv Infection ◽  
Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

Diversity of HIV-1 subtypes and transmitted drug-resistance mutations among minority HIV-1 variants in a Turkish cohort

2021 ◽  
Vol 19 ◽  
Author(s):  
Rabia Can Sarinoglu ◽  
Uluhan Sili ◽  
Ufuk Hasdemir ◽  
Burak Aksu ◽  
Guner Soyletir ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Treatment Naïve ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

Background: The World Health Organization (WHO) recommends the surveillance of transmitted drug resistance mutations (TDRMs) to ensure the effectiveness and sustainability of HIV treatment programs. Objective: Our aim was to determine the TDRMs and evaluate the distribution of HIV-1 subtypes using and compared next-generation sequencing (NGS) and Sanger-based sequencing (SBS) in a cohort of 44 antiretroviral treatment-naïve patients. Methods: All samples that were referred to the microbiology laboratory for HIV drug resistance analysis between December 2016 and February 2018 were included in the study. After exclusions, 44 treatment-naive adult patients with a viral load of >1000 copies/mL were analyzed. DNA sequencing for reverse transcriptase and protease regions was performed using both DeepChek ABL single round kit and Sanger-based ViroSeq HIV-1 Genotyping System. The mutations and HIV-1 subtypes were analyzed using the Stanford HIVdb version 8.6.1 Genotypic Resistance software, and TDRMs were assessed using the WHO surveillance drug-resistance mutation database. HIV-1 subtypes were confirmed by constructing a maximum-likelihood phylogenetic tree using Los Alamos IQ-Tree software. Results: NGS identified nucleos(t)ide reverse transcriptase inhibitor (NRTI)-TDRMs in 9.1% of the patients, non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI)-TDRMs in 6.8% of the patients, and protease inhibitor (PI)-TDRMs in 18.2% of the patients at a detection threshold of ≥1%. Using SBS, 2.3% and 6.8% of the patients were found to have NRTI- and NNRTI-TDRMs, respectively, but no major PI mutations were detected. M41L, L74I, K65R, M184V, and M184I related to NRTI, K103N to NNRTI, and N83D, M46I, I84V, V82A, L24I, L90M, I54V to the PI sites were identified using NGS. Most mutations were found in low-abundance (frequency range: 1.0% - 4.7%) HIV-1 variants, except M41L and K103N. The subtypes of the isolates were found as follows; 61.4% subtype B, 18.2% subtype B/CRF02_AG recombinant, 13.6% subtype A, 4.5% CRF43_02G, and 2.3% CRF02_AG. All TDRMs, except K65R, were detected in HIV-1 subtype B isolates.. Conclusion: The high diversity of protease site TDRMs in the minority HIV-1 variants and prevalence of CRFs were remarkable in this study. All minority HIV-1 variants were missed by conventional sequencing. TDRM prevalence among minority variants appears to be decreasing over time at our center.

scholarly journals Transmitted drug resistance mutations and subtype diversity among HIV-1 sero-positive voluntary blood donors in Accra, Ghana

2020 ◽  
Author(s):  
Billal Musah Obeng ◽  
Evelyn Yayra Bonney ◽  
Lucy Asamoah-Akuoko ◽  
Nicholas Israel Nii-Trebi ◽  
Gifty Mawuli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Blood Donors ◽  
Transmitted Drug Resistance ◽  
Nucleotide Sequencing ◽  
Plasma Samples ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Subtype B ◽  
Major Drug ◽  
Hiv 1

Abstract Background: Detection of HIV-1 transmitted drug resistance (TDR) and subtype diversity (SD) are public health strategies to assess current HIV-1 regimen and ensure effective therapeutic outcomes of ART among HIV-1 patients. Globally, limited data exist on TDR and SD among blood donors. In this study, drug resistance mutations and subtype diversity among HIV-1 sero-positive blood donors in Accra, Ghana was characterized.Methods: Purposive sampling method was used to collect 81 HIV sero-positive blood samples from the Southern Area Blood Center and confirmed by serology as HIV-1 and/or HIV-2. Viral RNA was only extracted from plasma samples confirmed as HIV-1 positive. Complementary DNA (cDNA) was synthesized using the RNA as a template and subsequently amplified by nested PCR with specific primers. The expected products were verified, purified and sequenced. Neighbor-joining tree with the Kimura’s 2-parameter distances was generated with the RT sequences using Molecular Evolutionary Genetic Analysis version 6.0 (MEGA 6.0).Results: Out of the 81 plasma samples, 60 (74%) were confirmed as HIV-1 sero-positive by INNO-LIA HIVI/II Score kit with no HIV-2 and dual HIV-1/2 infections. The remaining samples, 21 (26%) were confirmed as HIV sero-negative. Of the 60 confirmed positive samples, (32) 53% and (28) 50% were successfully amplified in the RT and PR genes respectively. Nucleotide sequencing of amplified samples revealed the presence of major drug resistance mutations in two (2) samples; E138A in one sample and another with K65R. HIV-1 Subtypes including subtypes A, B, CRF02_AG and CRF09_cpx were found. Conclusion: This study found major drug resistance mutations, E138A and K65R in the RT gene that confer high level resistance to most NNRTIs and NRTI respectively. CRF02_AG was most predominant, the recorded percentage of subtype B and the evolutionary relationship inferred by phylogenetic analysis suggest possible subtype importation. The data obtained would inform the selection of drugs for ART initiation to maximize therapeutic options in drug-naïve HIV-1 patients in Ghana.

scholarly journals Identification and Characterization of BMS-955176, a Second-Generation HIV-1 Maturation Inhibitor with Improved Potency, Antiviral Spectrum, and Gag Polymorphic Coverage

2016 ◽  
Vol 60 (7) ◽  
pp. 3956-3969 ◽  
Author(s):  
Beata Nowicka-Sans ◽  
Tricia Protack ◽  
Zeyu Lin ◽  
Zhufang Li ◽  
Sharon Zhang ◽  
...  
Keyword(s):  
Human Serum ◽  
Second Generation ◽  
Mononuclear Cells ◽  
Integrase Inhibitor ◽  
Wild Type Virus ◽  
Peripheral Blood Mononuclear ◽  
Subtype B ◽  
Maturation Inhibitor ◽  
Hiv 1

ABSTRACTBMS-955176 is a second-generation human immunodeficiency virus type 1 (HIV-1) maturation inhibitor (MI). A first-generation MI, bevirimat, showed clinical efficacy in early-phase studies, but ∼50% of subjects had viruses with reduced susceptibility associated with naturally occurring polymorphisms in Gag near the site of MI action. MI potency was optimized using a panel of engineered reporter viruses containing site-directed polymorphic changes in Gag that reduce susceptibility to bevirimat (including V362I, V370A/M/Δ, and T371A/Δ), leading incrementally to the identification of BMS-955176. BMS-955176 exhibits potent activity (50% effective concentration [EC50], 3.9 ± 3.4 nM [mean ± standard deviation]) toward a library (n= 87) ofgag/prrecombinant viruses representing 96.5% of subtype B polymorphic Gag diversity near the CA/SP1 cleavage site. BMS-955176 exhibited a median EC50of 21 nM toward a library of subtype B clinical isolates assayed in peripheral blood mononuclear cells (PBMCs). Potent activity was maintained against a panel of reverse transcriptase, protease, and integrase inhibitor-resistant viruses, with EC50s similar to those for the wild-type virus. A 5.4-fold reduction in EC50occurred in the presence of 40% human serum plus 27 mg/ml of human serum albumin (HSA), which corresponded well to anin vitromeasurement of 86% human serum binding. Time-of-addition and pseudotype reporter virus studies confirm a mechanism of action for the compound that occurs late in the virus replication cycle. BMS-955176 inhibits HIV-1 protease cleavage at the CA/SP1 junction within Gag in virus-like particles (VLPs) and in HIV-1-infected cells, and it binds reversibly and with high affinity to assembled Gag in purified HIV-1 VLPs. Finally,in vitrocombination studies showed no antagonistic interactions with representative antiretrovirals (ARVs) of other mechanistic classes. In conclusion, BMS-955176 is a second-generation MI with potentin vitroanti-HIV-1 activity and a greatly improved preclinical profile compared to that of bevirimat.

scholarly journals Prevalence of resistance mutations related to integrase inhibitor S/GSK1349572 in HIV-1 subtype B raltegravir-naive and -treated patients

2011 ◽  
Vol 66 (7) ◽  
pp. 1481-1483 ◽  
Author(s):  
I. Malet ◽  
M. Wirden ◽  
S. Fourati ◽  
D. Armenia ◽  
B. Masquelier ◽  
...  
Keyword(s):  
Integrase Inhibitor ◽  
Resistance Mutations ◽  
Subtype B ◽  
Hiv 1

scholarly journals HIV CRF07_BC is Independently Associated With Slower Disease Progression Than Subtype B in Chinese Patients: A Retrospective Observational Cohort Study

2021 ◽  
Author(s):  
Jingrong Ye ◽  
Yiming Shao ◽  
Hongyan Lu
Keyword(s):  
Disease Progression ◽  
Multivariable Analysis ◽  
Risk Groups ◽  
Transmission Risk ◽  
Chinese Patients ◽  
Data Set ◽  
Subtype B ◽  
Observational Cohort ◽  
Hiv Diversity ◽  
Epidemiological Information

Abstract HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count <200 cells/µL) in patients with HIV subtype B, CRF01_AE, and CRF07_BC. Of the 20,663 sequences, 9,156 (44.3%) were CRF01_AE. CRF07_BC was responsible for 28.3% of infections, followed by B (13.9%). In multivariable analysis, the risk of AIDSAD differed significantly according to HIV subtype (OR for CRF07_BC vs. B: 0.46, 95% CI 0.39─0.53), age (OR for ≥65 years vs. <18 years: 4.3 95% CI 1.81─11.8), and transmission risk groups (OR for man who have sex with man vs. heterosexual: 0.67 95% CI 0.6─0.75). These findings suggest that HIV diversity in China is constantly evolving and gaining complexity. CRF07_BC is less pathogenic than subtype B, while CRF01_AE is as pathogenic as B.

scholarly journals Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers

2015 ◽  
Vol 90 (6) ◽  
pp. 2806-2817 ◽  
Author(s):  
Javier Guenaga ◽  
Viktoriya Dubrovskaya ◽  
Natalia de Val ◽  
Shailendra K. Sharma ◽  
Barbara Carrette ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Small Animal ◽  
Subtype C ◽  
Disulfide Linkage ◽  
Vaccine Candidates ◽  
Subtype B ◽  
Subtype A ◽  
Induced Changes ◽  
Hiv 1 ◽  
Hiv Diversity

ABSTRACTDue to high viral diversity, an effective HIV-1 vaccine will likely require Envs derived from multiple subtypes to generate broadly neutralizing antibodies (bNAbs). Soluble Env mimics, like the native flexibly linked (NFL) and SOSIP trimers, derived from the subtype A BG505 Env, form homogeneous, stable native-like trimers. However, other Env sequences, such as JRFL and 16055 from subtypes B and C, do so to a lesser degree. The high-resolution BG505 SOSIP crystal structures permit the identification and redesign of Env elements involved in trimer stability. Here, we identified structure trimer-derived (TD) residues that increased the propensity of the subtype B JRFL and subtype C 16055 Env sequences to form well-ordered, homogenous, and highly stable soluble trimers. The generation of these spike mimics no longer required antibody-based selection, positive or negative. Using the redesigned subtype B and C trimer representatives as respective foundations, we further stabilized the NFL TD trimers by engineering an intraprotomer disulfide linkage in the prebridging sheet, I201C-A433C (CC), that locks the gp120 in the receptor nontriggered state. We demonstrated that this disulfide pair prevented CD4 induced-conformational rearrangements in NFL trimers derived from the prototypic subtype A, B, and C representatives. Coupling the TD-based design with the engineered disulfide linkage, CC, increased the propensity of Env to form soluble highly stable spike mimics that are resistant to CD4-induced changes. These advances will allow testing of the hypothesis that such stabilized immunogens will more efficiently elicit neutralizing antibodies in small-animal models and primates.IMPORTANCEHIV-1 displays unprecedented global diversity circulating in the human population. Since the envelope glycoprotein (Env) is the target of neutralizing antibodies, Env-based vaccine candidates that address such diversity are needed. Soluble well-ordered Env mimics, typified by NFL and SOSIP trimers, are attractive vaccine candidates. However, the current designs do not allow most Envs to form well-ordered trimers. Here, we made design modifications to increase the propensity of representatives from two of the major HIV subtypes to form highly stable trimers. This approach should be applicable to other viral Envs, permitting the generation of a repertoire of homogeneous, highly stable trimers. The availability of such an array will allow us to assess if sequential or cocktail immune strategies can overcome some of the vaccine challenges presented by HIV diversity.

HIV-1 subtype variability and transmitted drug resistance in a culturally diverse population in Western Sydney, New South Wales, Australia

Sexual Health ◽  
2020 ◽  
Vol 17 (4) ◽  
pp. 377
Author(s):  
Daniel Richardson ◽  
Hubert Chan ◽  
Rohan Bopage ◽  
David A. Lewis ◽  
Shailendra Sawleshwarkar ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Culturally Diverse ◽  
Hiv Transmission ◽  
Transmitted Drug Resistance ◽  
Diverse Population ◽  
Subtype B ◽  
Sexually Transmissible Infections ◽  
Treatment Naïve ◽  
Relative Prevalence ◽  
Hiv 1

Abstract Background Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) is an important contributor to antiretroviral treatment failure, and is associated with HIV-1 transmission among men who have sex with men (MSM), non-MSM clusters and individuals diagnosed with concurrent sexually transmissible infections (STI). Western Sydney has a culturally diverse population, with a high proportion of non-Australian-born individuals. This study describes the prevalence of TDR and non-B HIV-1 subtypes in a clinic-based population. Methods: A clinic database was examined for all newly diagnosed treatment-naïve HIV-1 patients and information on their HIV-1 resistance and subtype, demographics including country of birth and diagnosis of a bacterial sexually transmissible infection was collected. Results: Data were available from 74/79 individuals (62 cis-male, 16 cis-female and 1 transgender woman). Of the 74 genotypes, the prevalence of non-B subtypes and TDR was 43/74 (58%; 95%CI = 46.9–69.3) and 14/74 (19%; 95%CI = 10.0 to 27.8). It was also found that 30/79 (38%) had a concurrent bacterial STI. TDR was associated with subtype B infection (OR 3.53; 95%CI = 1.41–8.82; P = 0.007) and being born in Australia (OR 12.0; 95%CI = 2.45–58.86; P = 0.002). Conclusion: The relative prevalence of non-B HIV-1 subtypes and TDR is higher in Western Sydney than in the rest of Australia. TDR is associated with subtype B HIV-1 and being Australian born, suggesting ongoing local transmission. This highlights the diversity of the HIV epidemic locally and the need for interventions to prevent ongoing HIV transmission.

scholarly journals Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations

2009 ◽  
Vol 53 (11) ◽  
pp. 4869-4878 ◽  
Author(s):  
Rajin Shahriar ◽  
Soo-Yon Rhee ◽  
Tommy F. Liu ◽  
W. Jeffrey Fessel ◽  
Anthony Scarsella ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Previous Treatment ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Viral Subtypes ◽  
Hiv 1

ABSTRACT The spectrum of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) mutations selected by antiretroviral (ARV) drugs requires ongoing reassessment as ARV treatment patterns evolve and increasing numbers of protease and RT sequences of different viral subtypes are published. Accordingly, we compared the prevalences of protease and RT mutations in HIV-1 group M sequences from individuals with and without a history of previous treatment with protease inhibitors (PIs) or RT inhibitors (RTIs). Mutations in protease sequences from 26,888 individuals and in RT sequences from 25,695 individuals were classified according to whether they were nonpolymorphic in untreated individuals and whether their prevalence increased fivefold with ARV therapy. This analysis showed that 88 PI-selected and 122 RTI-selected nonpolymorphic mutations had a prevalence that was fivefold higher in individuals receiving ARVs than in ARV-naïve individuals. This was an increase of 47% and 77%, respectively, compared with the 60 PI- and 69 RTI-selected mutations identified in a similar analysis that we published in 2005 using subtype B sequences obtained from one-fourth as many individuals. In conclusion, many nonpolymorphic mutations in protease and RT are under ARV selection pressure. The spectrum of treatment-selected mutations is changing as data for more individuals are collected, treatment exposures change, and the number of available sequences from non-subtype B viruses increases.

scholarly journals The changing HIV-1 genetic characteristics and transmitted drug resistance among recently infected population in Yunnan, China

2018 ◽  
Vol 146 (6) ◽  
pp. 775-781 ◽  
Author(s):  
M. Chen ◽  
M. H. Jia ◽  
Y. L. Ma ◽  
H. B. Luo ◽  
H. C. Chen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Management Strategies ◽  
Recent Common Ancestor ◽  
Transmitted Drug Resistance ◽  
Subtype C ◽  
Effective Population ◽  
Genetic Characteristics ◽  
Infected Population ◽  
Subtype B ◽  
Hiv 1

AbstractMultiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.

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